Orchestration of Hippocampal Information Encoding by the Piriform Cortex

Abstract

The hippocampus utilizes olfactospatial information to encode sensory experience by means of synaptic plasticity. Odor exposure is also a potent impetus for hippocampus-dependent memory retrieval. Here, we explored to what extent the piriform cortex directly impacts upon hippocampal information processing and storage. In behaving rats, test-pulse stimulation of the anterior piriform cortex (aPC) evoked field potentials in the dentate gyrus (DG). Patterned stimulation of the aPC triggered both long-term potentiation (LTP > 24 h) and short-term depression (STD), in a frequency-dependent manner. Dual stimulation of the aPC and perforant path demonstrated subordination of the aPC response, which was nonetheless completely distinct in profile to perforant path-induced DG plasticity. Correspondingly, patterned aPC stimulation resulted in somatic immediate early gene expression in the DG that did not overlap with responses elicited by perforant path stimulation. Our results support that the piriform cortex engages in specific control of hippocampal information processing and encoding. This process may underlie the unique role of olfactory cues in information encoding and retrieval of hippocampus-dependent associative memories.

Keywords: dentate gyrus; hippocampus; in vivo; olfactory system; rodent; synaptic plasticity.

Figure 1

Electrode locations and comparison of electrophysiological responses evoked in the DG following aPC, or perforant path stimulation. (A) The recording electrode was positioned in the granule cell layer of the DG (red) by evoking potentials during depth profile recordings via a stimulation electrode placed in the perforant path (dashed green arrow). To ensure accurate placement of the electrode in the aPC (blue), it was first used to record responses during depth profile recordings via a stimulation electrode placed in the OB (dashed green arrow). The aPC electrode was subsequently used as a stimulation electrode, so that aPC–DG generated responses could be studied (solid green arrow). Coronal rat brain drawings, shown here, were modified from Paxinos and Watson (1998, 2005). Photomicrographs of Nissl-stained sections show placement of the stimulation electrode in the aPC (upper photo) and of the recording electrode in the DG (lower photo). Scale bars: 500 μm. (B) Input–output relationships for fEPSPs (aPC and DG) or PSs (DG only) were obtained using a stimulus intensity range of 100 to 900 μA for aPC–DG (squares, n = 6) and perforant path–DG (circles, n = 5). (C) Representative fEPSPs for both pathways evoked at increasing intensities: 1) 100 μA, 2) 300 μA, 3) 500 μA, 4) 700 μA, and 5) 900 μA. (D) Basal synaptic transmission of aPC–DG evoked responses remained stable with regard to both fEPSP amplitude and slope over a 24 h period (n = 9). Insets show representative fEPSPs evoked by test-pulse stimulation at the timepoints (1–4) indicated. Calibration: Vertical bar: 1 mV, horizontal bar: 5 ms. B, D mean ± SEM.

Figure 2

HFS applied to the aPC induces LTP in the hippocampus. HFS at 100 Hz induces LTP in the DG, when applied either as (A) 4 trains of 100 pulses or (B) 1 train of 100 pulses (n = 10) to the aPC. The arrow indicates the timepoint at which HFS was applied. Insets show analog examples of fEPSPs evoked prior to (1), 5 min after (2), and 4 h after (3) HFS. Calibration: Vertical bar: 1 mV, horizontal bar: 5 ms. A–C mean ± SEM.

Figure 3

Patterned stimulation of the aPC in the frequency range of beta oscillations, as well as paired-pulse LFS, induces synaptic plasticity in the hippocampus. (A,B) Stimulation of the aPC at 30 Hz (A, n = 8) or 15 Hz (B, n = 8) results in slow-onset potentiation in the DG of behaving rats. Insets show representative fEPSPs evoked prior to (1), 5 min following (2), and 4 h after (3) patterned stimulation. (C–D) Stimulation (C) at 3 Hz (n = 9) or (D) at 1 Hz (n = 8) of the aPC fails to change synaptic transmission in the DG. Insets: Representative fEPSPs evoked prior to (1) and 4 h after (2) test-pulse stimulation (left set of analogs) or patterned stimulation (right set of analogs). (E) Paired-pulse LFS (1 Hz, 900 pulse pairs) of the aPC induces STD in the DG (n = 9). Insets: Analog examples of fEPSPs evoked at the timepoints indicated either prior to (1) or after (2, 3) LFS. Calibration: Vertical bar: 1 mV, horizontal bar: 5 ms. A–E mean ± SEM. The arrow in each graph indicates the timepoint at which patterned stimulation was applied.

Figure 4

Stimulation of the perforant path (PP) overrides plasticity induced by piriform cortex activation. Induction of hippocampal synaptic plasticity by stimulation of the aPC or PP results in an increase of IEG expression in the DG. (A) Potentials were evoked in the DG by stimulating the aPC. LFS (1 Hz, 900 pulse pairs) of the aPC results in synaptic depression of aPC–DG responses. LFS of the PP results in a modest, slow-onset potentiation of aPC–DG responses. “Simultaneous” LFS of both the PP (n = 6) and aPC (n = 6) results in the predomination of the PP-mediated plasticity response at aPC–DG responses: a synaptic response resulted that was not significantly different from aPC–DG responses triggered by LFS of the PP “alone”. (B) Potentials were evoked in the DG by stimulating the PP. LFS of the aPC and/or PP results in synaptic depression in the PP-DG synapses (n = 7, each). The arrow indicates the timepoint at which LFS was applied. (C–D) Representative fEPSPs evoked prior to (1), 5 min after (2), and 4 h after LFS (3). Calibration: Vertical bar: 1 mV, horizontal bar: 5 ms. (E) 4',6-diamidino-2-phenylindole (DAPl)-stained section of the rat hippocampus showing the dorsal DG regions that were analyzed in the IEG study (red squares). (F) The IEGs, Arc, and Homer1a were examined in the brains of animals that received consecutive LFS of the aPC and PP, or received test-pulse stimulation under the same test conditions (controls). Somatic Homer1a expression reflects aPC stimulation and somatic Arc expression reflects PP stimulation. IEG expression in the upper blade of the DG is significantly increased after LFS of either the aPC (Homer1a) or the PP (Arc), compared with test-pulse stimulated controls (n = 6, each). (G) LFS of the aPC does not significantly alter Homer1a expression in the lower blade of the DG, whereas Arc mRNA levels increase in this region after LFS of the PP (compared with controls, all n = 6). (H–I) Photomicrographs of (H) the upper blade and (I) the lower blade of the DG showing Homer1a mRNA (green), Arc mRNA (red), and DAPI-stained nuclei of DG granule cells (blue) following LFS or test-pulse stimulation (controls). Homer1a mRNA positive nuclei are indicated by a white arrow and Arc mRNA positive nuclei are indicated by a gray arrow. Images were taken using a 63× objective. A–B, F–G mean ± SEM. F–G * = significance.